Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein

Author:

Aifantis Iannis1,Pivniouk Vadim I.2,Gärtner Frank3,Feinberg Jacqueline1,Swat Wojciech3,Alt Frederick W.3,von Boehmer Harald1,Geha Raif S.2

Affiliation:

1. Institut National de la Santé et Recherche Medicale (INSERM) U373, Hôpital Necker Enfants-Malades, Paris cedex 15, France

2. Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115

3. Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Abstract

Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4−CD8− double-negative (DN) thymocytes into CD4+CD8+ double-positive (DP) cells and for TCR-β allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76−/− mice are arrested at the CD25+CD44− DN stage. Here we show that SLP-76−/− DN thymocytes express the pre-TCR on their surfaces and that introduction of a TCR-α/β transgene into the SLP-76−/− background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCR-β rearrangement in SLP-76−/− TCR-transgenic mice or in single CD25+CD44− DN cells from SLP-76−/− mice indicates an essential role of SLP-76 in TCR-β allelic exclusion.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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